Journal of Central Nervous System Disease最新文献

{"title":"Hippocampal vulnerability to hyperhomocysteinemia worsens pathological outcomes of mild traumatic brain injury in rats.","authors":"Flaubert Tchantchou,&nbsp;Ru-Ching Hsia,&nbsp;Adam Puche,&nbsp;Gary Fiskum","doi":"10.1177/11795735231160025","DOIUrl":"https://doi.org/10.1177/11795735231160025","url":null,"abstract":"<p><strong>Background: </strong>Mild traumatic brain injury (mTBI) generally resolves within weeks. However, 15-30% of patients present persistent pathological and neurobehavioral sequelae that negatively affect their quality of life. Hyperhomocysteinemia (HHCY) is a neurotoxic condition derived from homocysteine accumulation above 15 μM. HHCY can occur in diverse stressful situations, including those sustained by U.S. active-duty service members on the battlefield or during routine combat practice. Mild-TBI accounts for more than 80% of all TBI cases, and HHCY exists in 5-7% of the general population. We recently reported that moderate HHCY exacerbates mTBI-induced cortical injury pathophysiology, including increased oxidative stress. Several studies have demonstrated hippocampus vulnerability to oxidative stress and its downstream effects on inflammation and cell death.</p><p><strong>Objective: </strong>This study aimed to assess the deleterious impact of HHCY on mTBI-associated hippocampal pathological changes. We tested the hypothesis that moderate HHCY aggravates mTBI-induced hippocampal pathological changes.</p><p><strong>Methods: </strong>HHCY was induced in adult male Sprague-Dawley rats with a high methionine dose. Rats were then subjected to mTBI by controlled cortical impact under sustained HHCY. Blood plasma was assessed for homocysteine levels and brain tissue for markers of oxidative stress, blood-brain barrier integrity, and cell death. Endothelial cell ultrastructure was assessed by Electron Microscopy and working memory performance using the Y maze test.</p><p><strong>Results: </strong>HHCY increased the hippocampal expression of nitrotyrosine in astroglial cells and decreased tight junction protein occludin levels associated with the enlargement of the endothelial cell nucleus. Furthermore, HHCY altered the expression of apoptosis-regulating proteins α-ii spectrin hydrolysis, ERK1/2, and AKT phosphorylation, mirrored by exacerbated mTBI-related hippocampal neuronal loss and working memory deficits.</p><p><strong>Conclusion: </strong>Our findings indicate that HHCY is an epigenetic factor that modulates mTBI pathological progression in the hippocampus and represents a putative therapeutic target for mitigating such physiological stressors that increase severity.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":"15 ","pages":"11795735231160025"},"PeriodicalIF":4.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/97/10.1177_11795735231160025.PMC9996738.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9155757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nerve ultrasound reference values in children and adolescents: Echogenicity and influence of anthropometric factors including hand volume.","authors":"Ifirae Yusuf,&nbsp;Hannah Mork,&nbsp;Bernhard Erdlenbruch,&nbsp;Peter Dieter Schellinger,&nbsp;Jörg Philipps","doi":"10.1177/11795735231195778","DOIUrl":"https://doi.org/10.1177/11795735231195778","url":null,"abstract":"<p><strong>Background: </strong>Nerve cross-sectional area (CSA) reference values in high-resolution ultrasound for children and adolescents are influenced by demographic and anthropometric factors such as age, height and weight.</p><p><strong>Objectives: </strong>The influence of hand volume as an additional morphometric factor was evaluated and nerve echogenicity was analyzed in a prospective cross-sectional study.</p><p><strong>Methods: </strong>CSA were measured in 30 healthy children and adolescents from 2 to 17 years in the median, ulnar, radial, tibial, peroneal and sural nerves. Height, weight, age, handedness and gender were recorded, the volume of the hands was measured using the water displacement method. The intra-nerve CSA variability (INV), left/right ratios and absolute differences were calculated. Age groups were compared by the Kruskal-Wallis test. The influence of demographic factors was analyzed using Spearman correlation and multiple linear regression. Echogenicity and fraction of black were determined for each nerve segment.</p><p><strong>Results: </strong>Nerve CSA values were consistently lower than those reported for adults and correlated in all measured nerve sites with age, height, weight and hand volume. Weight showed the highest correlation coefficient (R = .95) with the best fitting model predicting CSA. Correlation coefficients were higher in a linear than in a logarithmic model. Ratios were stable, the absolute differences increased with age and were significantly different between age groups. Most nerves showed a mixed or hypoechogenic pattern in echogenicity analysis, hyperechogenicity is less frequently observed.</p><p><strong>Conclusions: </strong>Nerve CSA in children and adolescents is lower than in adults and increases proportionally during growth with a constant INV and left/right ratio in different age groups. Weight and age are predominant anthropometric factors predicting nerve size. Hand volume is correlated with nerve size, but does not predict CSA independently. Echogenicity can provide additional information on nerve structure.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":"15 ","pages":"11795735231195778"},"PeriodicalIF":4.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/3c/10.1177_11795735231195778.PMC10446961.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and COVID-19: A Systematic Review.","authors":"Omid Mirmosayyeb,&nbsp;Elham Moases Ghaffary,&nbsp;Mohammad S Dehghan,&nbsp;Hamed Ghoshouni,&nbsp;Sara Bagherieh,&nbsp;Mahdi Barzegar,&nbsp;Vahid Shaygannejad","doi":"10.1177/11795735231167869","DOIUrl":"https://doi.org/10.1177/11795735231167869","url":null,"abstract":"<p><strong>Background: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an uncommon neurological disease affecting the central nervous system (CNS). Numerous neurological disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), acute transverse myelitis (ATM), and MOGAD, have been reported following the COVID-19 infection during the current COVID-19 pandemic. On the other hand, it has been suggested that patients with MOGAD may be at greater risk for infection (particularly in the current pandemic).</p><p><strong>Objective: </strong>In this systematic review, we gathered separately 1) MOGAD cases following COVID-19 infection as well as 2) clinical course of patients with MOGAD infected with COVID-19 based on case reports/series.</p><p><strong>Methods: </strong>329 articles were collected from 4 databases. These articles were conducted from inception to March 1^st, 2022.</p><p><strong>Results: </strong>Following the screening, exclusion criteria were followed and eventually, 22 studies were included. In 18 studies, a mean ± SD time interval of 18.6 ± 14.9 days was observed between infection with COVID-19 and the onset of MOGAD symptoms. Symptoms were partially or completely recovered in a mean of 67 days of follow-up.Among 4 studies on MOGAD patients, the hospitalization rate was 25%, and 15% of patients were hospitalized in the intensive care unit (ICU).</p><p><strong>Conclusion: </strong>Our systematic review demonstrated that following COVID-19 infection, there is a rare possibility of contracting MOGAD. Moreover, there is no clear consensus on the susceptibility of MOGAD patients to severe COVID-19. However, obtaining deterministic results requires studies with a larger sample size.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":"15 ","pages":"11795735231167869"},"PeriodicalIF":4.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/27/10.1177_11795735231167869.PMC10063869.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9595996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of interaction between verteporfin and yes-associated protein 1/transcriptional coactivator with PDZ-binding motif-TEA domain pathway on the progression of isocitrate dehydrogenase wild-type glioblastoma.","authors":"Mahmoud Osama,&nbsp;Muhammed Amir Essibayi,&nbsp;Mona Osama,&nbsp;Ismail A Ibrahim,&nbsp;Mostafa Nasr Mostafa,&nbsp;Murat Şakir Ekşi","doi":"10.1177/11795735231195760","DOIUrl":"https://doi.org/10.1177/11795735231195760","url":null,"abstract":"<p><p>Verteporfin and 5-ALA are used for visualizing malignant tissue components in different body tumors and as photodynamic therapy in treating isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM). Additionally, verteporfin interferes with Yes-associated protein 1 (YAP)/Transcriptional coactivator with PDZ-binding motif - TEA domain (TAZ-TEAD) pathway, thus inhibiting the downstream effect of these oncogenes and reducing the malignant properties of GBM. Animal studies have shown verteporfin to be successful in increasing survival rates, which have led to the conduction of phase 1 and 2 clinical trials to further investigate its efficacy in treating GBM. In this article, we aimed to review the novel mechanism of verteporfin's action, the impact of its interaction with YAP/TAZ-TEAD, its effect on glioblastoma stem cells, and its role in inducing ferroptosis.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":"15 ","pages":"11795735231195760"},"PeriodicalIF":4.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/b7/10.1177_11795735231195760.PMC10439684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10304411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationships between neuroglial and neuronal changes in Alzheimer's disease, and the related controversies II: <b>gliotherapies and multimodal therapy</b>.","authors":"Adolfo Toledano-Díaz,&nbsp;M Isabel Álvarez,&nbsp;Adolfo Toledano","doi":"10.1177/11795735221123896","DOIUrl":"https://doi.org/10.1177/11795735221123896","url":null,"abstract":"<p><p>Since the original description of Alzheimer´s disease (AD), research into this condition has mainly focused on assessing the alterations to neurons associated with dementia, and those to the circuits in which they are involved. In most of the studies on human brains and in many models of AD, the glial cells accompanying these neurons undergo concomitant alterations that aggravate the course of neurodegeneration. As a result, these changes to neuroglial cells are now included in all the \"pathogenic cascades\" described in AD. Accordingly, astrogliosis and microgliosis, the main components of neuroinflammation, have been integrated into all the pathogenic theories of this disease, as discussed in this part of the two-part monograph that follows an accompanying article on gliopathogenesis and glioprotection. This initial reflection verified the implication of alterations to the neuroglia in AD, suggesting that these cells may also represent therapeutic targets to prevent neurodegeneration. In this second part of the monograph, we will analyze the possibilities of acting on glial cells to prevent or treat the neurodegeneration that is the hallmark of AD and other pathologies. Evidence of the potential of different pharmacological, non-pharmacological, cell and gene therapies (widely treated) to prevent or treat this disease is now forthcoming, in most cases as adjuncts to other therapies. A comprehensive AD multimodal therapy is proposed in which neuronal and neuroglial pharmacological treatments are jointly considered, as well as the use of new cell and gene therapies and non-pharmacological therapies that tend to slow down the progress of dementia.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221123896"},"PeriodicalIF":4.8,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/9d/10.1177_11795735221123896.PMC9666878.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40699653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central nervous system, spinal root ganglion and brachial plexus involvement in leprosy: A prospective study.","authors":"Sumit Verma,&nbsp;Ravindra Kumar Garg,&nbsp;Imran Rizvi,&nbsp;Hardeep Singh Malhotra,&nbsp;Neeraj Kumar,&nbsp;Amita Jain,&nbsp;Swastika Suvirya,&nbsp;Anit Parihar,&nbsp;Rajesh Verma,&nbsp;Praveen Kumar Sharma,&nbsp;Shweta Pandey,&nbsp;Ravi Uniyal,&nbsp;Shantanu Prakash","doi":"10.1177/11795735221135477","DOIUrl":"https://doi.org/10.1177/11795735221135477","url":null,"abstract":"<p><strong>Background: </strong>Leprosy is primarily a disease of peripheral nerves. Some isolated case reports and case series have communicated imaging changes in the central nervous system (CNS) and brachial plexus in patients with leprosy.</p><p><strong>Objectives: </strong>To study the neuroimaging abnormalities in patients with lepra bacilli-positive neuropathy in the context of CNS, spinal root ganglion, and brachial plexus.</p><p><strong>Design: </strong>Prospective observational study.</p><p><strong>Methods: </strong>We screened newly-diagnosed patients with multibacillary leprosy presenting with neuropathy. Patients with bacilli-positive sural nerve biopsies were included in the study and subjected to magnetic resonance imaging (MRI) of the brain and spinal cord.</p><p><strong>Results: </strong>A total of 54 patients with bacteriologically confirmed multibacillary leprosy were screened; <i>Mycobacterium leprae</i> was demonstrated in the sural nerve biopsies of 29 patients. Five patients (5/29; 17.24%) had MRI abnormalities in CNS, spinal root ganglion, and/or brachial plexus. Three patients had MRI changes suggestive of either myelitis or ganglionitis. One patient had T2/FLAIR hyperintensity in the middle cerebellar peduncle while 1 had T2/FLAIR hyperintensity in the brachial plexus.</p><p><strong>Conclusion: </strong>CNS, spinal root ganglion, and brachial plexus are involved in patients with leprous neuropathy. Immunological reaction against <i>M leprae</i> antigen might be a plausible pathogenetic mechanism for brachial plexus and CNS imaging abnormalities.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221135477"},"PeriodicalIF":4.8,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/eb/10.1177_11795735221135477.PMC9583215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience.","authors":"Julian Perncezky,&nbsp;Johann Sellner","doi":"10.1177/11795735221135485","DOIUrl":"https://doi.org/10.1177/11795735221135485","url":null,"abstract":"<p><p>The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody blocks the α4β1 integrin-mediated leukocyte-endothelial interaction and thereby inhibits the migration of immune cells to the brain parenchyma. However, treatment with natalizumab carries the risk of progressive multifocal leukoencephalopathy (PML). This potentially lethal side effect is a significant limitation for treatment initiation and long-term therapy. Natalizumab is given intravenously or subcutaneously in the standard dose of 300 mg every 4 weeks, allowing drug concentrations at levels that ensure continuous α4β1 integrin receptor saturation on the surface of immune cells. Extended-interval dosing (EID) is an emerging treatment approach that aims to mitigate the natalizumab-related PML risk by prolonging the standard infusion intervals to 6 weeks or even more. This treatment approach may abrogate the PML risk due to improved immune surveillance within the central nervous system while maintaining clinical efficacy. Moreover, even an individual interval dosing can be envisioned based on the availability of a biomarker that is capable of monitoring both safety and efficacy aspects. This review summarizes the early and encouraging evidence for EID from observational and randomized-controlled trials and discusses current limitations and upcoming challenges for introducing a tailored treatment approach.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221135485"},"PeriodicalIF":4.8,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/c2/10.1177_11795735221135485.PMC9580073.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of endovascular thrombectomy in patients with severe cerebral venous thrombosis: A meta-analysis.","authors":"Gaurav Nepal,&nbsp;Sanjeev Kharel,&nbsp;Riwaj Bhagat,&nbsp;Megan A Coghlan,&nbsp;Jayant K Yadav,&nbsp;Stella Goeschl,&nbsp;Rajan Lamichhane,&nbsp;Subash Phuyal,&nbsp;Rajeev Ojha,&nbsp;Gentle S Shrestha","doi":"10.1177/11795735221131736","DOIUrl":"https://doi.org/10.1177/11795735221131736","url":null,"abstract":"<p><strong>Background: </strong>Cerebral venous thrombosis (CVT) is a rare thrombotic condition which is traditionally treated with anti-coagulation therapy. Subsets of patients with severe CVT have been treated with endovascular thrombectomy (EVT). Despite the high estimated mortality associated with severe CVT, there has been only one randomized control trial done regarding safety and efficacy of EVT in severe CVT compared to standard medical management. Evidence in this area is lacking.</p><p><strong>Objective: </strong>The aim of this systematic review is to analyze all existing literature and generate robust information regarding the role of EVT in the management of patients with severe CVT.</p><p><strong>Methods: </strong>This systematic review and meta-analysis followed PRISMA guideline. PubMed, Embase, Google Scholar, and CNKI were searched for eligible studies from 2007 to 2021. Safety and efficacy of EVT were evaluated by meta-analyzing recanalization status, the good functional outcome at follow-up, recurrent CVT, new hematoma. A pooled proportion with a 95% confidence interval was derived from a meta-analysis of various outcomes (CI).</p><p><strong>Results: </strong>A total of 33 studies comprising 610 patients treated with EVT were included for analysis which comprised one randomized control trial, one prospective study and 31 retrospective studies. Based on pooled data, 85% of patients had good functional outcome, 62% had complete recanalization, 5% had all-cause mortality, and 3% had catheter related complications. The efficacy outcomes in this analysis had a significant heterogeneity and a subgroup analysis was also done to explain these findings. The minimum time of follow up was 3 months and varied EVT techniques were used across the studies.</p><p><strong>Conclusion: </strong>This meta-analysis suggests EVT may be safe and efficacious in treating patients with severe CVT.</p><p><strong>Registration: </strong>Our protocol was registered with PROSPERO: International prospective register of systematic reviews with the registration number CRD42021254760.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221131736"},"PeriodicalIF":4.8,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/5a/10.1177_11795735221131736.PMC9530583.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33492899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Neurological Manifestations Associated With SARS-CoV-2 in Children: A Case Series.","authors":"Josef Finsterer","doi":"10.1177/11795735221123915","DOIUrl":"https://doi.org/10.1177/11795735221123915","url":null,"abstract":"DECLARATION OF CONFLICTING INTERESTS: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. FUNDING: The author(s) received no financial support for the research, authorship, and/or publication of this article.","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221123915"},"PeriodicalIF":4.8,"publicationDate":"2022-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/b5/10.1177_11795735221123915.PMC9478691.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats.","authors":"Abdullah Md Sheikh,&nbsp;Shozo Yano,&nbsp;Shingo Mitaki,&nbsp;Shatera Tabassum,&nbsp;Shuhei Yamaguchi,&nbsp;Atsushi Nagai","doi":"10.1177/11795735221123910","DOIUrl":"https://doi.org/10.1177/11795735221123910","url":null,"abstract":"<p><strong>Background: </strong>Rho-kinase inhibition in a rat middle cerebral artery occlusion (MCAO) model is reported to improve neurological functions and decrease infarction size.</p><p><strong>Objective: </strong>The objective of this study is to investigate the underlying mechanisms of such improvement by evaluating the effects of Rho-kinase inhibition on astrocytes and microglial accumulation and activation in this condition.</p><p><strong>Methods: </strong>Adult male Sprague-Dawley (SD) rats were used to generate the MCAO model, which received an I.P injection of a chemical Rho-kinase inhibitor (Fasudil- 5 mg/kg/day) or vehicle (PBS) for 2 and 4 days.</p><p><strong>Results: </strong>Fasudil treatment significantly decreased the stroke volumes and water content in the lesion areas, as revealed by MRI. Immunostaining and Western blotting results demonstrated that Fasudil significantly decreased the levels of Aquaporin-4, a water channel protein. The number of GFAP⁺ astrocytes and Iba-1⁺ macrophage/microglia was decreased in the lesion areas. Proinflammatory transcription factor NF-κB protein levels were decreased in the Fasudil group 2 days after MCAO. Also, proinflammatory mediators including TNF-α, IL-1β, and iNOS levels were decreased. In vitro migration study using a human microglial cell line (HMO6) confirmed the inhibitory effects of Fasudil on the process. Fasudil also decreased combined IL-1β and IFNγ-induced NF-κB nuclear translocation in HMO6. Moreover, Fasudil transiently decreased combined IL-1β and IFNγ-induced iNOS, TNFα, and IL-1β mRNA levels in HMO6.</p><p><strong>Conclusion: </strong>Our study demonstrates the inhibitory effects of Rho-kinase on NF-κB-mediated glial activation and cerebral edema, which might be a promising therapeutic target in acute cerebral ischemia conditions.</p>","PeriodicalId":15218,"journal":{"name":"Journal of Central Nervous System Disease","volume":" ","pages":"11795735221123910"},"PeriodicalIF":4.8,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/f0/10.1177_11795735221123910.PMC9465613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40358840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}